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Cilia‐localized LKB 1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney
Author(s) -
Viau Amandine,
Bienaimé Frank,
Lukas Kamile,
Todkar Abhijeet P,
Knoll Manuel,
Yakulov Toma A,
Hofherr Alexis,
Kretz Oliver,
Helmstädter Martin,
Reichardt Wilfried,
Braeg Simone,
Aschman Tom,
Merkle Annette,
Pfeifer Dietmar,
Dumit Verónica I,
Gubler MarieClaire,
Nitschke Roland,
Huber Tobias B,
Terzi Fabiola,
Dengjel Jörn,
Grahammer Florian,
Köttgen Michael,
Busch Hauke,
Boerries Melanie,
Walz Gerd,
Triantafyllopoulou Antigoni,
Kuehn E Wolfgang
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798615
Subject(s) - medicine , chemokine , library science , receptor , computer science
Polycystic kidney disease ( PKD ) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB 1 and several ciliopathy‐related proteins including NPHP 1 and PKD 1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL 2 in tubular epithelial cells. Deletion of LKB 1 or PKD 1 in mouse renal tubules elevates CCL 2 expression in a cell‐autonomous manner and results in peritubular accumulation of CCR 2 + mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis.